Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies.

Loss-of-function of protein A20, encoded by TNFAIP3, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of TNFAIP3 variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous de novo variant in his TNFAIP3 gene (c.740C＞T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a de novo missense variant resulting in a loss-of-function of TNFAIP3, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.

Conversion of drylands to paddy fields on former wetlands restores soil organic carbon by accumulating labile carbon fractions in the Sanjiang Plain, northeast China.

BACKGROUND: Since the 1990s, drylands have been extensively converted to rice paddy fields on the former wetlands in the Sanjiang Plain of northeast China. However, the influence of this successiveland-use change from native wetlands to drylands to rice paddy fields on soil organic carbon (C) dynamics remains unexplored. Here, we compared the difference in soil organic C stock among native wetlands, drylands, and paddy fields, and then used a two-step acid hydrolysis approach to examine the effect of this land-use change on labile C I (LPI-C), labile C II (LPII-C), and recalcitrant C (RP-C) fractions at depths of 0-15 cm, 15-30 cm, and 30-50 cm. RESULTS: Soil organic C stock at a depth of 0-50 cm was reduced by 79% after the conversion of wetlands to drylands but increased by 24% when drylands were converted to paddy fields. Compared with wetlands, paddy fields had 74% lower soil organic C stock at a depth of 0-50 cm. The conversion of wetlands to drylands reduced the concentrations of LPI-C, LPII-C, and RP-C fractions at each soil depth. However, land-use change from drylands to paddy fields only increased the concentrations of LPI-C and LPII-C fractions at the 0-15 cm and 30-50 cm depths. CONCLUSION: The conversion of drylands to paddy lands on former wetlands enhances the soil organic C stock by promoting labile C fraction accumulation, and labile C fractions are more sensitive to this successive land-use change than recalcitrant C fractions in the Sanjiang Plain of northeast China. © 2022 Society of Chemical Industry.

Effects of long-term nitrogen addition on dissolved organic matter characteristics in a temperate wetland of Northeast China.

Dissolved organic matter (DOM) plays an indispensable role in ecosystem services and functions in wetlands. While most wetlands have undergone increased nitrogen (N) loading due to intensive human activities, the response of DOM characteristics to long-term N addition remains unexplored. In this study, we assessed the changes in dissolved organic carbon (DOC), NH4+, NO3-, dissolved organic N (DON), dissolved total N (DTN), and dissolved total phosphorus (DTP) in surface water and soil pore water at 15 cm depth after 10 years of N addition at four levels (0, 60, 120, and 240 kg N hm-2 year-1) in a freshwater marsh of Northeast China. We also examined the effect of N addition on DOM aromaticity and humification by measuring the specific UV absorbance at 254 nm (SUVA254), the color per C unit (C/C ratio), and the fulvic acid/humic acid ratio (E4/E6 ratio). Our results showed that N addition significantly altered DOM properties, but the direction and magnitude of these changes generally did not vary with the N addition level. During the growing season, DOC, NH4+, NO3-, DON, and DTN concentrations in both surface water and soil pore water were increased by N addition. Accordingly, N addition increased the DOC/DTP and DTN/DTP ratios but decreased the DOC/DTN ratio in surface water and soil pore water. In addition, the SUVA254 value and C/C ratio increased, while the E4/E6 ratio reduced after N addition in surface water and soil pore water, indicating increases in DOM aromaticity and humification. These observations suggest that long-term N addition changes DOM characteristics by causing stoichiometric imbalances and increasing recalcitrant compounds in temperate freshwater wetlands, which may then deteriorate water quality, alter microbial-mediated ecological processes, and impact downstream aquatic ecosystem structures.

Overexpression of CUGBP1 is associated with the progression of non-small cell lung cancer.

The multifunctional RNA-binding protein CUGBP1 regulates multiple aspects of nuclear and cytoplasmic messenger RNA (mRNA) processing, including splicing, stabilization, and translation of mRNAs. Previous studies have shown that CUGBP1 is overexpressed in non-small-cell lung cancer (NSCLC) tissues, but the pathological functions of CUGBP1 in tumorigenesis and development are unknown. Here, we provide the first evidence demonstrating the clinicopathological significance of CUGBP1 in NSCLC. Using immunohistochemistry, the levels of CUGBP1 expression in NSCLC tissues and adjacent non-cancerous tissues were examined and determined to be associated with differentiation. Short hairpin RNA-induced downregulation of CUGBP1 promoted apoptosis and decreased proliferation in the A549 NSCLC cell line. Moreover, Western blot analysis indicated that the depletion of CUGBP1 increased the protein levels of cyclin D1, BAD, BAX, Jun D, and E-cadherin, while the cyclin B1 level decreased. Knockdown of CUGBP1 decreased ß-catenin and vimentin levels and increased E-cadherin expression, suggesting that CUGBP1 may contribute significantly to epithelial to mesenchymal transition (EMT) progression. These results demonstrate the importance of CUGBP1 in the biological and pathological functions of NSCLC and indicate its potential as a therapeutic target for NSCLC.

Bronchial thermoplasty for severe asthma: potential mechanisms and response markers.

Severe asthma (SA) poses a significant challenge to management and treatment, leading to a reduced quality of life and a heavy burden on society and healthcare resources. Bronchial thermoplasty (BT) has emerged as a non-pharmacological intervention for SA, demonstrating its efficacy and safety in improving patients' quality of life and reducing exacerbation rates for over a decade. In particular, BT encounters various obstacles in its clinical application. Since asthma is characterized by high heterogeneity, not all patients derive effective outcomes from BT. Furthermore, current knowledge of markers that indicate response to BT remains limited. Recent research has shed light on the intricate mechanism of action of BT, which extends beyond simple smooth muscle ablation. Therefore, to enhance the clinical practice and implementation of BT, this paper aims to elucidate the mechanism of action and identify potential markers associated with BT response.

A review of a non-drug treatment for asthma to better understand the potential mechanisms and markers of the treatmentA non-drug treatment for asthma: Severe asthma leads to a low quality of life and places a heavy burden on society and healthcare resources. A non-drug treatment for asthma called bronchial thermoplasty is a technique that uses high temperatures to remove excess airway muscle. Its efficacy and safety in improving asthma patients' quality of life have been demonstrated for more than a decade. Barriers to the treatment development: When it comes to clinical application, bronchial thermoplasty faces several barriers. Asthma is characterized by high variability, and not all patients have good outcomes from bronchial thermoplasty. Understanding of the effectiveness of bronchial thermoplasty remains limited. New insights into how the treatment works: Recent research has found that the effect of bronchial thermoplasty is complicated and goes beyond simple muscle removal. What is the aim of this review: To improve the use of bronchial thermoplasty by discussing its effects on the body and identifying ways to measure how effective the treatment is.

The Sequential and Systemic Administration of BMP-2 and SDF-1α Nanocapsules for Promoting Osteoporotic Fracture Healing.

OBJECTIVE: The objective of this study was to investigate the use of the nanocapsule sequential delivery of BMP-2 and SDF-1α through the peripheral circulatory system to promote the healing of osteoporotic fractures. METHODS: Based on increased vascular permeability in the early hematoma environment around the fracture and the presence of a large number of matrix metalloproteinase MMPs in the inflammatory environment, we designed MMP-sensitive nanocapsules which were formed viain situ free-radical polymerization on the surface of grow factors with 2-(methacryloyloxy) ethyl phosphorylcholine (MPC) and the bisacryloylated VPLGVRTK peptide. The antiphagic effect and biological activity of the growth factors for the nanomicrocapsule delivery system were tested by cell experiments. The 36 SD rats with an osteoporotic fracture model were randomly divided into six groups (A, B, C, D, E, and F). In this paper, the nanocapsules loaded with BMP-2 and SDF-1 are represented as n (BMP-2) and n (SDF-1α). In the six groups, the following different combinations of growth factors were injected into the bone defect site on days 1 and 3 after bone defect surgery: in group A, n (SDF-1α) combined with n (SDF-1α); in group B, n (BMP-2) combined with n (BMP-2); in group C, n (SDF-1α) + n (BMP-2) combined with n (SDF-1α) + n (BMP-2); in group D, n (SDF-1α) combined with n (BMP-2); in group E, n (BMP-2) combined with n (SDF-1α); in group F, nanocapsules without growth factor were used as the control group. Micro-CT was used to observe the effect of n(BMP-2) and n(SDF-1α) sequential delivery inearly healing in osteoporotic fractures. Finally, in this study, we evaluated the safety of the nanocapsules delivery system by detecting ectopic osteogenesis and inflammatory responses in animals. RESULTS: Nanocapsules have low toxicity and protect the integrity and biological activity of growth factors. The results confirmed that nanocapsules could still be effectively targeted to the fracture site on days 1, 3, and 7 after intravenous administration. Growth factors encapsulated in nanocapsules have better bone repair results than natural growth factors. In particular, groups C and D had the best bone repair results than other groups.In vivo experiments confirmed that nanocapsules did not cause significant ectopic osteogenesis and inflammation. CONCLUSION: The results confirmed that the special vascular permeability and inflammatory factor microenvironment of the fracture site could be used to deliver two growth factors with a synergistic effect through venous circulation, which could better promote the healing process of osteoporotic fracture.

An in situ catechol functionalized ε-polylysine/polyacrylamide hydrogel formed by hydrogen bonding recombination with high mechanical property for hemostasis.

In situ hydrogel has attracted widely attention in hemostasis due to its ability to match irregular defects, but its application is limited by insufficient mechanical strength and long gelation time. Although some specifical in situ chemically cross-linked hydrogels could be fast formed and exhibit high mechanical strength, they unable to absorb blood. Hence their applications were further limited in emergency hemostasis usage. In this study, a robust hydrogel formed by hydration of powders was developed using multiple hydrogen bonds crosslinking. Here, catechol groups modified ε-polylysine (PL-CAT) and polyacrylamide (PAAM) were used to construct the PL-CAT/PAAM hydrogel. This hydrogel could be formed within 7 s to adhere and seal bleeding sites. The catechol groups endowed the hydrogel outstanding adhesive strength, which was 3.5 times of fibrin glue. Besides, the mechanical performance of in-situ PL-CAT/PAAM hydrogel was explored and the results showed that the hydrogel exhibited high compressive strength (0.47 MPa at 85% strain). Most importantly, the blood loss of wound treated with PL-CAT/PAAM hydrogel powders was 1/7 of untreated group, indicating the hydrogel's excellent hemostatic effect. And the cytotoxicity studies indicated that the PL-CAT/PAAM hydrogel had low toxicity. To summarize, this hydrogel could be a potential hemostatic material in emergency situations.

Chronic nitrogen addition promotes dissolved organic carbon accumulation in a temperate freshwater wetland.

Temperate wetlands have been undergoing increased nitrogen (N) inputs in the past decades, yet its influence on dissolved organic carbon (DOC) dynamics is still elusive in these ecosystems. Here, using a field multi-level N addition (0, 6, 12, and 24 g N m-2 year-1) experiment, we investigated the changes in aboveground plant biomass, DOC production from plant litters, DOC biodegradation, and DOC concentration in surface water and soil pore water (0-15 cm depth) following 10 years of N addition in a freshwater marsh of Northeast China. We observed that, irrespective of N addition levels, N addition caused an increase in DOC production from plant litters under both non-flooded and flooded conditions. Conversely, DOC biodegradation was inhibited by N addition in both surface water and soil pore water. Because of enhanced DOC production from plant litters and declined DOC biodegradation, N addition elevated DOC concentration in surface water and soil pore water across the growing season. In addition, long-term N addition increased aboveground plant biomass, but decreased species richness. Our results suggest that long-term N enrichment promotes DOC accumulation through the contrasting effects on litter-derived DOC production and microbial decomposition of DOC in temperate wetlands.

[Spatial Distribution and Pollution Evaluation of Carbon, Nitrogen, and Phosphorus in Sediments of Zhushan Bay at Taihu Lake].

To reveal the distribution characteristics of carbon, nitrogen and phosphorus in the sediments of Zhushan Bay at Taihu Lake, sedimentary columns were collected and sliced by 2 cm vertically from ten sampling points in three sections of Zhushan Bay. The content of total nitrogen (TN), total phosphorus (TP), and total organic carbon (TOC) were determined for each slice to reveal their horizontal and vertical distribution. The results showed that:spatially, the content of TN, TP, and TOC increased in the surface sediments of Zhushan Bay from the open lake area to the bay, and inside the bay these indexes were significantly higher than in the open lake area (P<0.01). The content of TN, TP, and TOC in the surface sediments in the bay (section A) were 1.53 mg·g-1, 1.55 mg·g-1, and 11.31 mg·g-1, respectively, while in the surface sediments near the open lake (section C) they were only 0.75 mg·g-1, 0.57 mg·g-1, and 6.70 mg·g-1, respectively. Vertically, a feature of surficial enrichment was shown, and the contents of carbon, nitrogen and phosphorus in all three sections showed a decreasing trend with increase of depth. The contents of TN, TP and TOC in the surface sediments are 2-3 times, 2-5 times, and 2-3 times those in the bottom sediments, respectively. Generally, the average TP content in the sediment of Zhushan Bay is 0.93 mg·g-1, suggesting an apparent heavy pollution, while the average TN content is 1.11 mg·g-1 as slight pollution. According to the organic nitrogen index and comprehensive pollution index, the northern part of Zhushan Bay is suffering from heavy pollution, where the organic pollution is relatively strong. The TP pollution index is between 1.03 and 3.87, indicating heavy pollution in Zhushan Bay.

Ventana immunohistochemistry assay for anaplastic lymphoma kinase gene rearrangement detection in patients with non-small cell lung cancer: A meta-analysis.

BACKGROUND: The aim of this study was to evaluate the diagnostic value of Ventana immunohistochemistry (IHC) assay for anaplastic lymphoma kinase (ALK) gene rearrangement screening in patients with non-small cell lung cancer (NSCLC). METHODS: Open published studies that reported the diagnostic performance of Ventana IHC assay for ALK gene rearrangement detection in NSCLC patients were extracted from PubMed, Embase, Google scholar, Wanfang, and China National Knowledge Infrastructure. The general information and number of true positive (tp), false positive (fp), false negative (fn), and true negative (tn) cases identified by Ventana IHC assay were extracted. The diagnostic sensitivity, specificity, positive likelihood ratio (+lr), negative likelihood ratio (-lr), diagnostic odds ratio (dor) and the summary receiver operating characteristic (ROC) curve were calculated using Stata 11.0 software. RESULTS: Ten studies, including 240 ALK positive and 1973 ALK negative NSCLC patients were included in this meta-analysis. The pooled diagnostic sensitivity, specificity, +lr, -lr, and dor were 0.94 (95% confidence interval [CI] 0.85-0.98), 1.00 (95% CI 0.99-1.00), 859.61 (95% CI 60.81-1200.00), 0.06 (95% CI 0.03-0.16), and 1400.00 (95% CI 813.29-23 000.00), respectively. The area under the ROC curve was 0.996 for Ventana IHC assay in detecting ALK gene rearrangement in NSCLC patients. CONCLUSION: The sensitivity and specificity of Ventana IHC assay for the detection of ALK gene rearrangement were high, thus Ventana IHC could substitute fluorescence in situ hybridization for the screening of ALK+ NSCLC patients.

Long-term phosphorus addition enhances the biodegradability of dissolved organic carbon in a nitrogen-limited temperate freshwater wetland.

Phosphorus (P) enrichment is expected to strongly influence dissolved organic carbon (DOC) biodegradation. However, the relationship between P availability and DOC biodegradation is largely unknown in nitrogen (N)-limited ecosystems. Here, we investigated the changes in the ratio of DOC to dissolved total nitrogen (DTN), specific UV absorbance at 254nm (SUVA254), and DOC biodegradation in surface water and soil pore water (0-15cm depth) following eight years of multi-level P addition (0, 1.2, 4.8, and 9.6gPm-2year-1) in an N-limited freshwater marsh in Northeast China. We found that P addition caused an increase in DOC biodegradation in surface water and soil pore water, irrespective of the P addition levels. Compared with the control treatment, the P addition rates of 1.2, 4.8, and 9.6gPm-2year-1 increased DOC biodegradation by 20.7%, 15.2%, and 14.5% in surface waters, and 11.3%, 9.4%, and 12.0% in soil pore waters, respectively. The DOC biodegradation was separately negatively correlated with the DOC:DTN ratio and SUVA254, indicating that the positive effect of P addition on DOC biodegradation was caused by the elevated N concentration and the reduced DOC aromaticity. Our findings suggest that P enrichment enhances the biodegradability of DOC through increased N availability and altered DOC chemical composition, which would accelerate DOC loss from the waters and alter ecosystem C balance in N-limited temperate wetlands.

Effect of long-term phosphorus addition on the quantity and quality of dissolved organic carbon in a freshwater wetland of Northeast China.

Understanding how P enrichment alters the quantity and quality of dissolved organic carbon (DOC) is important, because of their role in regulating the C cycle. Here, we established a four-level P addition experiment (0, 1.2, 4.8, and 9.6gPm-2year-1) in a N-limited freshwater wetland in the Sanjiang Plain, Northeast China. The aim of this study was to examine the effects of eight years of P addition on DOC concentration, SUVA254 (Abs254/DOC concentration, indicating the aromaticity of DOC), C:C ratio (Abs400/DOC concentration, indicating the proportion of colored humic substances in DOC), and E4:E6 ratio (Abs465/Abs665, indicating the molecular size of humic substances) in surface water and soil pore water (0-15cm depth) during the growing season (June through September). Our results showed similar changing trends in concentration and optical properties of DOC following eight years of P addition in the both surface water and soil pore water across the sampling dates. Generally, P addition decreased DOC concentration, SUVA254, and C:C ratio, and increased E4:E6 ratio, irrespective of P addition levels. These altered optical properties of DOC indicated that P addition decreased the molecular weight and aromaticity of DOC, and thus increased the quality of DOC. These results suggest P enrichment substantially reduces the quantity of DOC in N-limited temperate freshwater wetlands, and imply that increased DOC quality following P addition can further provide a positive feedback to decreased DOC pool.

The observation of abnormal signals in laser flash photolysis: a type of probable synchronized nuclear spin signals.

In laser flash photolysis (LFP) work, noise-like signals were observed together with transient absorption decay spectra in time domain. Analyzed results show that it is a valuable resonance spectrum of excited state molecules, in which four molecular cases are given here. We proposed that this kind signal might originate from nuclear or nuclear and electron spin resonance features in the excited molecules based on radio wave frequency spectrum levels and the significant interaction with static magnetic field.

Effects of P addition on plant C:N:P stoichiometry in an N-limited temperate wetland of Northeast China.

Phosphorus (P) enrichment induced by anthropogenic activities results in modified plant nutrient status, which potentially alters the stoichiometry of carbon (C), nitrogen (N), and P in plants. However, how increased P availability changes plant C:N:P stoichiometry at different hierarchical scales is unclear in N-limited ecosystems. In this study, we conducted a four-level P addition experiment (0, 1.2, 4.8, and 9.6gPm(-)(2)year(-1)) to elucidate the effect of P enrichment on plant C:N:P stoichiometric ratios at both the species and community levels in a freshwater wetland in the Sanjiang Plain, Northeast China. We found that species- and community-level plant C:N:P stoichiometry responded consistently to six years of P addition, although there was a shift in species dominance. Phosphorus addition increased plant N and P concentrations and thus decreased C:N, C:P, and N:P ratios irrespective of the P addition levels. These similar change trends at different scales resulted from the identical responses of plant N and P concentrations in different species to P addition. Moreover, plant N concentration exhibited an increasing trend with increasing P addition levels, whereas plant C:N ratio showed a declining trend. At the community level, P addition at the rates of 1.2, 4.8, and 9.6gPm(-2)year(-1) decreased the C:N ratio by 24%, 27%, and 34%; decreased the C:P ratio by 33%, 35%, and 38%; and decreased the N:P ratio by 12%, 10%, and 6%, respectively. Our results indicate that the stoichiometric responses to P addition are scale-independent, and suggest that altered plant C:N:P stoichiometry induced by P enrichment would stimulate organic matter decomposition and accelerate nutrient cycles in N-limited temperate freshwater wetlands.

Some properties of the interaction between 2,2'-diselenadibenzoic acid and serum albumins.

The binding of 2,2'-diselenadibenzoic acid to bovine serum albumin (BSA) and human serum albumin (HSA) was studied by using fluorescence spectroscopy. The measurement was performed in Tris-HCl buffer aqueous medium at pH = 7.40. The quenching constant at 303 K was (3.277 +/- 0.046) x 10(13) L mol(-1) s(-1) for BSA, and (3.946 +/- 0.002) x 10(12) L mol(-1) s(-1) for HSA. Decreased quenching was observed in association with increased temperature. Our findings show that the observed binding constant is dependent on the ionic strength of the medium. It is said that electrostatic interactions play a role in the binding of 2,2'-diselenadibenzoic acid to serum albumin, in addition to the hydrophobic association. The decrease of the linearity of S-V plot demonstrates reduced binding of ligand to the protein in the presence of anionic surfactants such as sodium dodecyl sulfate (SDS), which indicates that 2,2'-diselenadibenzoic acid most likely binds to the hydrophobic pockets within sub-domain IIA of serum albumin, the same site as SDS.

Responses of plant nutrient resorption to phosphorus addition in freshwater marsh of Northeast China.

Anthropogenic activities have increased phosphorus (P) inputs to most aquatic and terrestrial ecosystems. However, the relationship between plant nutrient resorption and P availability is still unclear, and much less is known about the underlying mechanisms. Here, we used a multi-level P addition experiment (0, 1.2, 4.8, and 9.6 g P m(-2) year(-1)) to assess the effect of P enrichment on nutrient resorption at plant organ, species, and community levels in a freshwater marsh of Northeast China. The response of nutrient resorption to P addition generally did not vary with addition rates. Moreover, nutrient resorption exhibited similar responses to P addition across the three hierarchical levels. Specifically, P addition decreased nitrogen (N) resorption proficiency, P resorption efficiency and proficiency, but did not impact N resorption efficiency. In addition, P resorption efficiency and proficiency were linearly related to the ratio of inorganic P to organic P and organic P fraction in mature plant organs, respectively. Our findings suggest that the allocation pattern of plant P between inorganic and organic P fractions is an underlying mechanism controlling P resorption processes, and that P enrichment could strongly influence plant-mediated biogeochemical cycles through altered nutrient resorption in the freshwater wetlands of Northeast China.